The overall goal of this project is to study spinal cord axonal degeneration in a mouse model using magnetic resonance imaging (MRI). In the central nervous system (CNS), the spinal cord acts as the major pathway between the peripheral nervous system and the brain. Damages to the spinal cord due to injuries, toxic exposure, or neurological diseases often cause axonal degeneration. One example is Multiple Sclerosis (MS). MS is characterized by demyelination and axonal damage, which leads to axonal degeneration. In MS patients, axonal degeneration plays an important role in the development of neurological disability and has been identified as the major determinant of irreversible neurological disability. To understand the precise mechanisms of axonal degeneration in MS and spinal cord injuries, several small animal models have been developed, such as the experimental allergic encephalomyelitis (EAE) model. Techniques that can non- invasively monitor the state of axonal degeneration will provide important information on the spatial and temporal profiles of pathogenesis, treatment efficacy, and axonal regeneration. Currently, non-invasive monitoring of axonal degeneration is difficult to achieve in the mouse. The miniature size of the mouse spinal cord (1approximately 2 mm in diameter) requires high spatial resolution. In this proposal, we will develop in vivo high resolution MRI techniques for quantitative measurement of tissue T2 (transverse relaxation time), averaged apparent diffusion constant (ADC,) and diffusion anisotropy in the mouse spinal cord. These techniques will then be used to characterize axonal degeneration in mice that undergo L4L5 dorsal radiculotomy. The results will then be correlated with ex vivo MR measurements and histopathology. [unreadable] [unreadable] [unreadable]